Gutenberg Open Science
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Item type: Item , Zeitschriftenaufsatz Access status: Open Access , Bringing exosomes into the game : current situation, opportunities, limitations and future perspectives(2025) Dikici, Emrah; Önal Acet, Burcu; Gül, Désirée; Kummer, Nina; Stauber, Roland H.; Odabaşi, Mehmet; Acet, ÖmürExosomes are microscopic vesicles secreted by cells, serving as carriers of diverse biological substances and playing an essential role in the communication between cells. When meticulously engineered, these small extracellular vesicles transform into highly effective delivery systems for therapeutic agents, enabling the targeted administration of active pharmaceutical ingredients to specific organs, tissues, and cells. Exosomes play an indispensable role in a myriad of biological processes, including intercellular communication, the regulation of gene expression, apoptosis, inflammation, immunity, as well as cell maturation and differentiation. The versatile role of exosomes is largely attributed to their intricate cargoes and composition, which encompasses nucleic acids, proteins, and lipids. In this review, we present a comprehensive overview of state-of-the-art characterization and isolation techniques used for the study of exosomes, especially for exosome-based biomedical applications. We will discuss the potential use of exosomes in personalized treatments, their interactions with other nanostructures focusing on the biomolecule corona, as well as the challenges and future expectations. In conclusion, this review provides evidence that we will witness extremely important functions and advances with innovative therapeutic and diagnostic applications of exosomes in the biomedical field.Item type: Item , Zeitschriftenaufsatz Access status: Open Access , Activity-dependent localization and dynamics of STIM1 and STIM2 at ER-PM contacts in hippocampal neurons(2025) Chhikara, Arun; Maciąg, Filip; Sorusch, Nasrin; Heine, MartinStromal interaction molecules (STIMs) are Ca2+ sensors within the endoplasmic reticulum (ER) plasma membrane (PM) that contribute to homeostatic functions in neurons. Upon depletion of Ca2+ from the ER, STIMs translocate to ER-PM junctions to contact the inner leaflet of the PM. Using single-particle tracking, we characterize the dynamic properties of endogenous STIM1 and STIM2 proteins in hippocampal neurons. STIMs form clusters in the somato-dendritic compartment but only transiently visit synapses. A substantial fraction of STIM2 proteins define ER-PM contacts under resting conditions and is dependent on the constitutive activity of NMDARs. STIM1 proteins are transiently recruited to ER-PM junctions only during strong activation of NMDARs. Activity-dependent confinement of STIM proteins is not influenced by CaV1.2 channel activity. We propose that STIM proteins fulfill a dominant structural function in neurons by regulating the size and frequency of ER-PM contacts to promote ER-PM communication along dendrites.Item type: Item , Zeitschriftenaufsatz Access status: Open Access , Simulating extractables and leachables in biopharmaceutical manufacturing to support safety assessment(2025) Bossong, Maximilian; Hauk, Armin; Pahl, Ina; Menzel, Roberto; Langguth, PeterThe use of single-use systems in the manufacturing of biopharmaceuticals raises concerns about the accumulation of process equipment-related leachables in their production and purification processes. However, this risk is mitigated by effective sinks in the manufacturing processes and dilution of product flow, for example, in tangential-flow-filtration. This paper presents a modeling approach that combines the release and adsorption of compounds with dynamic process conditions of biopharmaceutical processes. These calculations help assess process criticality by identifying sources but also low-risk processes and components regarding extractables and leachables accumulation. This approach can significantly reduce the necessity for resource-intensive practical testing, such as leachable studies, which may be impractical from an analytical perspective due to the complex matrices in biopharmaceutical process streams.